Metformin impacts the differentiation of mouse bone marrow cells into macrophages affecting tumour immunity

被引：4

作者：

Scafidi, Andrea ^{[1
,2
]}

Mogensen, Frida Lind-Holm ^{[1
,2
]}

Campus, Eleonora ^{[1
,2
]}

Pailas, Alexandros ^{[2
,3
]}

Neumann, Katrin ^{[3
]}

Legrave, Nathalie ^{[4
]}

Bernardin, Francois ^{[4
,5
]}

Pereira, Sandro L. ^{[4
,5
]}

Antony, Paul M. A. ^{[6
]}

Nicot, Nathalie ^{[7
,8
]}

Mittelbronn, Michel ^{[9
,10
,11
,12
,13
]}

Grunewald, Anne ^{[5
]}

Nazarov, Petr, V ^{[14
,15
]}

Poli, Aurelie ^{[1
]}

Van Dyck, Eric ^{[3
]}

Michelucci, Alessandro ^{[1
]}

机构：

[1] Luxembourg Inst Hlth, Dept Canc Res, Neuroimmunol Grp, L-1210 Luxembourg, Luxembourg

[2] Univ Luxembourg, Fac Sci Technol & Med, L-4365 Esch Sur Alzette, Luxembourg

[3] Luxembourg Inst Hlth, Dept Canc Res, DNA Repair & Chemoresistance, L-1210 Luxembourg, Luxembourg

[4] Luxembourg Inst Hlth, Dept Canc Res, Metabol Platform, L-1445 Strassen, Luxembourg

[5] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Mol & Funct Neurobiol Grp, L-4362 Esch Sur Alzette, Luxembourg

[6] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Bioimaging Platform, L-4362 Esch Sur Alzette, Luxembourg

[7] Luxembourg Inst Hlth, LuxGen Genome Ctr, L-3555 Dudelange, Luxembourg

[8] Lab Natl Sante, L-3555 Dudelange, Luxembourg

[9] Univ Luxembourg, Fac Sci Technol & Med, Dept Life Sci & Med, L-4367 Belvaux, Luxembourg

[10] Univ Luxembourg, Luxembourg Ctr Syst Biomed, L-4362 Esch Sur Alzette, Luxembourg

[11] Luxembourg Inst Hlth, Dept Canc Res, L-1210 Luxembourg, Luxembourg

[12] Luxembourg Ctr Neuropathol, Lab Natl Sante, L-3555 Dudelange, Luxembourg

[13] Natl Ctr Pathol, Lab Natl Sante, L-3555 Dudelange, Luxembourg

[14] Luxembourg Inst Hlth, Dept Med Informat, Bioinformat & AI Unit, L-1445 Strassen, Luxembourg

[15] Luxembourg Inst Hlth, Dept Canc Res, Multi Data Sci Res Grp, L-1445 Strassen, Luxembourg

来源：

HELIYON | 2024年 / 10卷 / 18期

关键词：

Luxembourg; Metformin; Macrophages; Phagocytosis; Anti-tumour; HIF1; alpha; Glycolysis; UP-REGULATION; HYPOXIA; POLARIZATION; ACTIVATION; PATHWAY; GENES;

D O I：

10.1016/j.heliyon.2024.e37792

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: Epidemiological studies suggest that metformin reduces the risk of developing several types of cancer, including gliomas, and improves the overall survival in cancer patients. Nevertheless, while the effect of metformin on cancer cells has been extensively studied, its impact on other components of the tumour microenvironment, such as macrophages, is less understood. Results: Metformin-treated mouse bone marrow cells differentiate into spindle-shaped macrophages exhibiting increased phagocytic activity and tumour cell cytotoxicity coupled with modulated expression of co-stimulatory molecules displaying reduced sensitivity to inflammatory cues compared with untreated cells. Transcriptional analyses of metformin-treated mouse bone marrow-derived macrophages show decreased expression levels of pro-tumour genes, including Tgfbi and Il1 beta, related to enhanced mTOR/HIF1 alpha signalling and metabolic rewiring towards glycolysis. Significance: Our study provides novel insights into the immunomodulatory properties of metformin in macrophages and its potential application in preventing tumour onset and in cancer immunotherapy.

引用

页数：17

共 82 条

[11]

Chen Z., 2023, J. Clin. Invest, V133

[12] Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling [J].

Cheng, Demin ;

Xu, Qi ;

Wang, Yue ;

Li, Guanru ;

Sun, Wenqing ;

Ma, Dongyu ;

Zhou, Siyun ;

Liu, Yi ;

Han, Lei ;

Ni, Chunhui .

JOURNAL OF TRANSLATIONAL MEDICINE, 2021, 19 (01)

[13] mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity [J].

Cheng, Shih-Chin ;

Quintin, Jessica ;

Cramer, Robert A. ;

Shepardson, Kelly M. ;

Saeed, Sadia ;

Kumar, Vinod ;

Giamarellos-Bourboulis, Evangelos J. ;

Martens, Joost H. A. ;

Rao, Nagesha Appukudige ;

Aghajanirefah, Ali ;

Manjeri, Ganesh R. ;

Li, Yang ;

Ifrim, Daniela C. ;

Arts, Rob J. W. ;

van der Meer, Brian M. J. W. ;

Deen, Peter M. T. ;

Logie, Colin ;

O'Neill, Luke A. ;

Willems, Peter ;

van de Veerdonk, Frank L. ;

van der Meer, Jos W. M. ;

Ng, Aylwin ;

Joosten, Leo A. B. ;

Wijmenga, Cisca ;

Stunnenberg, Hendrik G. ;

Xavier, Ramnik J. ;

Netea, Mihai G. .

SCIENCE, 2014, 345 (6204) :1579-+

[14] Hypoxic Enlarged Mitochondria Protect Cancer Cells From Apoptotic Stimuli [J].

Chiche, Johanna ;

Rouleau, Matthieu ;

Gounon, Pierre ;

Brahimi-Horn, M. Christiane ;

Pouyssegur, Jacques ;

Mazure, Nathalie M. .

JOURNAL OF CELLULAR PHYSIOLOGY, 2010, 222 (03) :648-657

[15] Metabolic programming of tumor associated macrophages in the context of cancer treatment [J].

Crezee, Thomas ;

Rabold, Katrin ;

de Jong, Lisanne ;

Jaeger, Martin ;

Netea-Maier, Romana T. .

ANNALS OF TRANSLATIONAL MEDICINE, 2020, 8 (16)

[16] Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition [J].

Crist, McKenzie ;

Yaniv, Benyamin ;

Palackdharry, Sarah ;

Lehn, Maria A. ;

Medvedovic, Mario ;

Stone, Timothy ;

Gulati, Shuchi ;

Karivedu, Vidhya ;

Borchers, Michael ;

Fuhrman, Bethany ;

Crago, Audrey ;

Curry, Joseph ;

Martinez-Outschoorn, Ubaldo ;

Takiar, Vinita ;

Wise-Draper, Trisha M. .

JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2022, 10 (11)

[17] Metformin coordinates with mesenchymal cells to promote VEGF-mediated angiogenesis in diabetic wound healing through Akt/mTOR activation [J].

Du, Fangzhou ;

Liu, Mengmeng ;

Wang, Jingwen ;

Hu, Lvzhong ;

Zeng, Dongao ;

Zhou, Shaocong ;

Zhang, Lixing ;

Wang, Meijia ;

Xu, Xi ;

Li, Chenglong ;

Zhang, Jingzhong ;

Yu, Shuang .

METABOLISM-CLINICAL AND EXPERIMENTAL, 2023, 140

[18] Human monocyte-derived macrophages are heterogenous: Proteomic profile of different phenotypes [J].

Eligini, S. ;

Brioschi, M. ;

Fiorelli, S. ;

Tremoli, E. ;

Bonfi, C. ;

Colli, S. .

JOURNAL OF PROTEOMICS, 2015, 124 :112-123

[19] Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia [J].

Fang, Hsin-Yu ;

Hughes, Russell ;

Murdoch, Craig ;

Coffelt, Seth B. ;

Biswas, Subhra K. ;

Harris, Adrian L. ;

Johnson, Randall S. ;

Imityaz, Hongxia Z. ;

Simon, M. Celeste ;

Fredlund, Erik ;

Greten, Florian R. ;

Rius, Jordi ;

Lewis, Claire E. .

BLOOD, 2009, 114 (04) :844-859

[20] Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications [J].

Feng, Jin ;

Wang, Xiaohui ;

Ye, Xiaochun ;

Ares, Irma ;

Lopez-Torres, Bernardo ;

Martinez, Marta ;

Martinez-Larranaga, Maria-Rosa ;

Wang, Xu ;

Anadon, Arturo ;

Martinez, Maria-Aranzazu .

PHARMACOLOGICAL RESEARCH, 2022, 177

← 1 2 3 4 5 6 7 8 9 →